intratumoral gene mediated cytotoxic immunotherapy in patients with resectable non-small cell lung cancer

Conditions: Lung Cancer

Summary: this is a phase i dose escalation study of can-2409 plus prodrug in patients with non-small cell lung cancer (nsclc). the primary clinical objective of the study is to evaluate the safety of can-2409 plus prodrug when combined with standard surgery for nsclc. the primary scientific objective is to determine the immunologic changes induced by can-2409 plus prodrug.

the purpose of this open-label, dose escalation clinical trial is to investigate the safety of can-2409 (aglatimagene besadenovec) plus prodrug prior to surgery in patients with nsclc. can-2409 is a viral immunotherapy approach which utilizes intratumoral administration to selectively induce tumor cell death and elicit both an innate and an adaptive systemic anti-tumor immune response against the injected tumor and uninjected metastases. local delivery enables these effects while aiming to minimize systemic toxicity. standard of care surgical resection will be performed about 3 weeks after the can-2409 injection. chemotherapy and/or radiation may begin 6-8 weeks after resection surgery. choice of chemotherapy depends on the treating oncologist. can-2409 (aglatimagene besadenovec) was previously known as adv-tk, and the combination of can-2409 plus prodrug was previously known as gmci.

Eligibility criteria:
inclusion criteria: * pathologically documented non-small cell carcinoma (cytology or histology) that is accessible via standard-of-care staging procedures: (1) ebus or (2) surgical approaches (eg mediastinoscopy, mediastinotomy or vats). * resectable with negative lymph nodes based on imaging with histologic confirmation at time of the staging procedure prior to adv-tk injection * the tumor must be 4cm or greater in diameter based on imaging * ecog performance status of 0 or 1. * granulocyte count (anc) ≥ 1,000/mm3 * peripheral lymphocyte count ≥ 500/mm3 * hemoglobin ≥ 9 g/dl * platelets ≥ 100,000/mm3 * total bilirubin ≤ 1.5 x upper limit of normal * sgot (ast) ≤ 3x upper limit of normal * serum creatinine \< 2mg/dl * calculated creatinine clearance \> 30ml/min * patients must give study specific informed consent prior to enrollment exclusion criteria: * radiotherapy and/or treatment with chemotherapeutic, cytotoxic, or immunologic agents within 4 weeks prior to infusion of the vector. * known immunodeficiency such as hiv infection * active liver disease, including known cirrhosis or active hepatitis * use of systemic corticosteroids (\>10 mg prednisone per day or equivalent) or other systemic immunosuppressive drugs * patient is pregnant or breast-feeding. female patients of childbearing age must have negative serum or urine pregnancy test within 1 week of beginning therapy. subjects must use acceptable means of birth control until 30 days after the vector injection. * presence of any other life-threatening illness, such as unstable angina, severe oxygen dependence, significant chronic obstructive pulmonary disease (copd), end-stage liver or renal disease. copd will be considered significant if disease limits activities of daily living, results in the inability to walk up 1 flight of stair, or requires home oxygen. * presence of known untreated brain metastases. * prior bone marrow transplants (including stem cells) except autologous stem cell transplant without immunosuppression is not considered an exclusion. * known sensitivity or allergic reactions to valacyclovir

Keywords: aglatimagene besadenovec can-2409 immunotherapy gmci adv-tk